IL-1 is a major pro-inflammatory cytokine that induces HIV transcription macrophages. The understanding of the regulation of IL-2 production would lead to possibilities to suppress its undesirable effects. HIV infection induces dementia in many patients. This dementia is related to the presence of HIV infected macrophages in the CNS. What causes the initial transcriptional activation of HIV in the brain, or the migration of infected cells, is not known, but it is possible that this is due to the presence of pro-inflammatory cytokines. Therefore we initiated studies to analyze the expression of pro-inflammatory cytokine genes (IL-1, TNFalpha) in the mouse brain. IL-1 has CNS effects. In a recent report, Saper et al. described IL-1 in neurons by immunohistology localized to areas involved in thermoregulation and sleep. We did not find IL-1 expressing cells in the normal brain by in situ hybridization. To resolve this apparent enigma IL-1 expression was studied in the normal embryonic, neonatal and adult, LPS injected, and germ-free (gnotobiotic) brains of mice by PCR analysis. The results suggest that under basal conditions, these genes are transcribed at low levels, detectable only by PCR analysis. However, i.v. exposure of the animal to known inducers of inflammatory cytokine production markedly increased the levels of IL-1 and TNFalpha mRNAs. These results suggest that pro-inflammatory cytokine production in the brain may be strongly affected by inflammatory processes elsewhere or by bacterial cell wall structures e.g. LPS, produced by normal gut flora or introduced through food and water intake. Thus, it is possible that careful anti- inflammatory treatment of AIDS patients would reduce the speed of dementia development.